PROJECT-002 - LEUKEMIA RESEARCH PROGRAM (LR) PROJECT SUMMARY / ABSTRACT The Leukemia Research (LR) Program within The Ohio State University Comprehensive Cancer Center (OSUCCC) is co-led by two physician scientists; Drs. John C. Byrd and Michael R. Grever who bring together 34 peer-reviewed funded members from 9 Departments and 5 Colleges (Engineering, Pharmacy, Medicine, Veterinary Medicine, and Arts & Sciences). The program is focused on the etiology, pathogenesis, prognosis, and treatment of leukemia with emphasis on acute myeloid leukemia (AML), human T-cell lymphotrophic virus l (HTLV-1) leukemia, large granular lymphocyte leukemia, hairy cell leukemia and chronic lymphocytic leukemia (CLL). LR Program-wide seminars, retreats, and disease-specific meetings provide an avenue for interaction among scientists and physicians to improve the quality of scientific discovery made through research. The LR Program integrates the use of novel technologies and translational and clinical support personnel provided through OSUCCC shared resources to facilitate impactful discoveries that ultimately have the potential to change the lives of patients with leukemia. LR Program discoveries span diagnostics through therapeutics, many of which are actively tested in both investigator initiated clinical trials and also NCI sponsored Phase I and II as well as cooperative group trials where our members have prominent leadership roles. The Specific Aims of LR Program include: 1) to integrate genetic, epigenetic, RNA/protein, non-coding RNAs, biochemical and immunosuppressive features of leukemic cells in order to enhance risk stratification and target identification; and 2) to foster preclinical and clinical development of epigenetic, targeted molecular, and immunologic therapeutics directed at the causes of leukemic transformation and progression. LR Program members have published 557 manuscripts of which 48% are inter-programmatic, 53% are intra- programmatic, 61% are multi-institutional; total collaborative publications are 93%. The Program has $8.7M in annual direct costs of peer-reviewed funding of which $6.1M (70%) is from the NCI, including strong programmatic funding in basic, translational, and clinical research. With regard to translational research, in five years the LR Program members have accrued 1,660 patients to interventional clinical trials, 100% of which were therapeutic accruals, and of those, 989, or 60%, were placed on investigator-initiated trials. Of the 1,660 patients accrued, 1,495 or 90% were on Phase I/II trials. LR Program members have led the development of two therapeutic agents (ibrutinib and idelalisib) that were recently FDA approved for leukemia. Additionally, LR Program members have developed two novel diagnostic tests that are now utilized in clinical practice. Our future plans consist of targeted recruitment, continued enhancement of collaborative efforts, better molecular classification of both AML and CLL for improvement in targeted therapies, and moving a number of preclinical and clinical observations onto novel clinical trials.